Employing the reproducible and carefully validated experimental animal model described previously we are studying the hepatic metabolism of pancreatic islet hormones glucagon, somatostatin and insulin. Studies completed have shown the importance of the liver in both glucagon and somatostatin metabolism. The role of the liver in insulin metabolism has been previously demonstrated and reconfirmed in these studies. Under basal conditions the liver clearly plays a major role in metabolism of these three islet peptides. Studies currently in progress are aimed at assessing if this degradative function of the liver can be modulated and if so what factors might modify this extraction. For example we have begun by studying the effects of feeding (e.g. glucose, or protein) and fasting on hepatic extraction of insulin and glucagon. Studies on the simultaneous hepatic and renal metabolism of insulin and glucagon and the relationship of these to one another are also currently in progress.